The precise regulation of protein activity is fundamental to life. A mechanism of regulation, found across protein classes, from enzymes, to motors, to signaling proteins, is allosteric control of an active site by a remote regulatory binding site.
Many proteins function like molecular machines that undergo mechanical movements in response to input signals. These signals can consist of changes in voltage, membrane tension, temperature or, most commonly, ligand concentration. Ligands provide information about events in the external world, or about the energetic or biosynthetic state of the cell, and can be as small as a proton or as large as a whole protein. In allostery, ligand binding induces a structural change of a sensor domain, which propagates to a functional domain of the protein and alters its behavior. Such conformational control can operate over long distances, crossing a membrane or passing from one protein to another in a complex.
Photochromic molecules have emerged as powerful optical tools to control protein and cellular function in neuroscience. Photoswitchable tethered ligands are covalently anchored to protein surfaces through photoisomerizable tethers. Photoswitching changes the length and geometry of the tether to alter the effective concentration of ligand at its binding site, thereby modulating protein function.
There is a need in the art for methods of regulating protein function.